This proposal outlines a three-year continuation and extension of work initiated by the candidate with the support of a Sloan Foundation and Department of Energy postdoctoral fellowship in Computational Molecular Biology. The objective of the candidate in submitting this proposal is to complete a research career transition to computational molecular biology. Three research projects are described. A Markov model of telomeric silencing in yeast A model for the development of a unique colony morphology in yeast A study of natural variation in yeast by analysis of mRNA expression data for glycolysis genes and modeling of the glycolytic pathway The first project, a study of telomeric silencing in yeast, is undertaken in collaboration with the laboratory of Daniel Gottschling at the Fred Hutchinson Cancer Research Center. The second, examining a unique colony morpholoy in yeast, is conducted under the auspices of the Gottschling laboratory and incorporates a significant laboratory training component for the candidate. The last project, a study of yeast natural variation, is an outgrowth of the candidate's collaboration with Maynard Olson and his laboratory at the University of Washington; this study will be conducted in collaboration with the laboratory of Leland Hartwell at the Fred Hutchinson Cancer Research Center. The proposal incorporates a career development plan for the candidate which includes formal coursework in genetics and biochemistry, training in laboratory techniques, participation in a short course on genomics, and attendance at conferences. Thomas Milac, the candidate, received the B.S. in physics and mathematics from Syracuse University in 1982, and the Ph.D. in applied mathematics (theoretical mechanics) from the University of Washington in 1995.